Synthesis and biological evaluation of new cyclopenteno[b]thiophene derivatives as local anesthetic and antiarrhythmic agents.
A series of ethyl 2-substituted amino-cyclopenteno[b]thiophen-3-carboxylates was synthesized as a carticaine analogues and evaluated for their local anesthetic and antiarrhythmic activity. Compounds ethyl 2-[1-oxo-2-(ethylamino)ethylamino]-(4a), ethyl 2-[1-oxo-2-(n-propylamino)-ethylamino]-(4c), ethyl 2-[1-oxo-2-(4-methylpiperazino)ethylamino]-(4e), ethyl 2-[1-oxo-2-(ethylamino)propylamino]-(5a) and ethyl 2-[1-oxo-2-(n-propylamino)propylamino]cyclopenteno[b]thiophen++ +-3-carboxylate (5c) proved to possess local anesthetic and antiarrhythmic activity comparable to carticaine and lidocaine. The active compounds exert their antiarrhythmic potency via blocking Na+ channels as in case of 5c or blocking Ca+2 channels as in case of 4a, 4c and 5c. Compound 4e exhibited a dual mechanism by blocking both Na+ and Ca+2 channels.
al-Obaid
A M
AM
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
el-Subbagh
H I
HI
al-Shabanah
O A
OA
Mahran
M A
MA
D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D002122:Calcium Chloride; D002355:Carticaine / Q000737:chemistry / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D010042:Ouabain; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000138:chemical synthesis*
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D013876:Thiophenes; D010042:Ouabain; D002355:Carticaine; D002122:Calcium Chloride